The xenobiotic dichloroacetate (DCA) is ubiquitous in our biosphere as a product of water chlorination and as a metabolite of certain industrial solvents and pharmaceuticals. As such, it has generated interest among environmental scientists as a potential human health hazard. However, DCA has long been used as an investigational drug for the treatment of several acquired or congenital disorders of intermediary metabolism, particularly genetic mitochondrial diseases that have a frequency in the general population of >1 in 5,000. Interest in its therapeutic potential has recently intensified, based on reports of its selective pro-apoptotic and antiproliferative actions in human cancers and in pulmonary arterial hypertension that have led to several early-phase clinical trials. In turn, the possibility of increased long-term exposure to DCA for the treatment of both rare and common diseases has heightened attention about its pharmacokinetics, biotransformation and chronic safety in humans.